Phase 2 Clinical Evaluation of Combination Immunotherapy for Renal Cell Carcinoma
Phase 2 Clinical Evaluation of Combination Immunotherapy for Renal Cell Carcinoma
This phase II trial tests adding VSV-IFNβ-NIS to standard of care ipilimumab and nivolumab for the treatment of clear cell renal cell carcinoma that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). A virus modified in the laboratory, such as VSV-IFNβ-NIS, may be able to kill tumor cells without damaging normal cells. Immunotherapy with monoclonal antibodies, such as ipilimumab and nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving VSV-IFNβ-NIS with ipilimumab and nivolumab may be effective for the treatment of advanced or metastatic clear cell renal cell carcinoma.
Inclusion Criteria:
Age ≥ 18 years
Disease Characteristics:
Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
Hemoglobin ≥ 9.0 g/dL (obtained ≤ 15 days prior to registration)
Absolute neutrophil count (ANC) ≥ 1500/mm^3 (obtained ≤ 15 days prior to registration)
Platelet count ≥ 100,000/mm^3 (obtained ≤ 15 days prior to registration)
Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (obtained ≤ 15 days prior to registration)
Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤ 3 x ULN (≤ 5 x ULN for patients with liver involvement) (obtained ≤ 15 days prior to registration)
Prothrombin time (PT)/international normalization ratio (INR)/activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN OR if patient is receiving anticoagulant therapy and INR or aPTT is within target range of therapy (≤ 5 x ULN for patients with liver involvement) (obtained ≤ 15 days prior to registration)
Serum creatinine ≤ 1.5 x upper limit of normal (ULN) OR creatinine clearance ≥ 50 ml/min using the chronic kidney disease epidemiology (CKD-EPI) creatinine equation (per National Kidney Foundation) (obtained ≤ 15 days prior to registration)
Negative pregnancy test done ≤ 8 days prior to registration, for persons of childbearing potential only
Provide written informed consent
Willingness to provide mandatory blood specimens for correlative research
Willingness to provide mandatory tissue specimens for correlative research
Willing to return to Mayo Clinic for follow-up (during the active monitoring phase of the study)
Exclusion Criteria:
Any of the following because this study involves an investigational agent, the genotoxic, mutagenic and teratogenic effects of which on the developing fetus and newborn are unknown:
Prior treatment for advanced or metastatic RCC [American Joint Committee on Cancer (AJCC) Stage IV]
History of portal vein thrombosis involving more than intrahepatic portal vein branches: thrombosis of the right or left portal vein branch or the bifurcation, partial or complete obstruction of the portal vein trunk
Has received a live vaccine ≤ 30 days prior to registration
Any of the following prior therapies:
New York Heart Association classification III or IV, known symptomatic coronary artery disease, or symptoms of coronary artery disease on systems review, or known cardiac arrhythmias [atrial fibrillation or supraventricular tachycardia (SVT)]
Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
Uncontrolled intercurrent illness including, but not limited to:
Current immunodeficiency or immunosuppression and receiving systemic corticosteroids at > 10mg/day prednisone or equivalent ≤ 1 week prior to registration.
Known history of the following:
Suspected active organ-threatening autoimmune disease including, but not limited to, inflammatory bowel disease, autoimmune hepatitis, lupus, or pneumonitis which can flare while receiving immune checkpoint inhibitor (ICI) treatment.
Non-infectious pneumonitis that required steroids, current pneumonitis, carcinomatous meningitis, or interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity
Known or ongoing illness or infection including:
Any active Grade 3 or higher [per the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version (v) 5.0] viral, bacterial, or fungal infection ≤ 2 weeks of registration.
Acute hepatitis B (HBV) or acute hepatitis C virus (HCV)
Patients known to be HIV positive and currently receiving antiretroviral therapy
Known history of active tuberculosis (TB) (bacillus tuberculosis)
Uncontrolled hypertension and/or diabetes
Clinically significant pulmonary disease (e.g., chronic obstructive pulmonary disease requiring hospitalization ≤ 3 months prior to treatment)
Receiving concurrent anti-cancer therapy (chemotherapy, immunotherapy, radiotherapy, or any other investigational agent or therapy considered investigational (used for a non-Food and Drug Administration (FDA) approved indication and in the context of a research investigation)
Known concurrent malignancy that is progressing or requires active treatment
History of myocardial infarction ≤ 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
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